In utero exposure of humans to high levels of ethanol can result in a variety of neurological anomalies collectively termed "alcohol related neurodevelopmental disorders" (ARND). Some of the hallmarks of observed cases of ARND bear a striking similarity to those seen in individuals with mutations in the cell adhesion molecule (CAM) L1. This has given rise to the hypothesis that L1 is a target for ethanol, and consistent with this idea, many L1-dependent functions including neuron migration, axon extension, axon fasciculation and myelination are particularly vulnerable to ethanol exposure. The overall goals of this grant are to determine the nature and mechanism of ethanol actions on L1-dependent axon extension. Specifically, the proposal is to examine the effects of ethanol on the surface expression, axonal polarization and membrane fluidity of L1, and to identify the mechanism by which ethanol decreases L1-dependent axon outgrowth. The data from this work will directly address the effects of fetal alcohol exposure on the development of normal neural connectivity, and will also have relevance for mechanisms of recovery following traumatic brain injury or stroke, where many developmentally regulated molecules become re-expressed and recovery of function is impaired by ethanol.